Sanofi

Here we have the usual forward looking statements. We would like to remind you that information presented in this call contains forward-looking statements which are subject to substantial risk and uncertainties that may cause actual results to differ materially. We encourage you to read the disclaimer in our slide presentation. In addition, we refer you to our Form 20F on File with the U.S. SEC and our French Universal Registration Document for description of these risk factors. As usual, we'll be making comments on our performance using constant exchange rates and other non-IFRS measures. Numbers used are in millions of euros and for Q4 or full year 2025 are not stated otherwise. Please turn to slide number four. First, we have a presentation, which is a little longer due to full year results. Then we will take your questions. We aim at keeping it all to one hour, perhaps a little bit more, including questions. We appreciate other companies are also reporting today. For the Q&A, we have Olivier, Ryan, and Thomas to cover our global businesses, as well as Roy, our general counsel, and Brendan, head of manufacturing and supply. For the Q&A, you can participate in two ways, either raise your hand in Zoom or submit your question using the Q&A feature. With all of this, I'll now hand you over to Paul.

Well, thank you, and hello, everyone. In 2025, we continue to develop into an R&D-driven, AI powered by a pharma company. Our strategic progress was supported by the completion of the appellate transaction, allowing us to reinvest proceeds into business development and M&A opportunities, while completing our 5 billion share buyback program. We've had a strong performance with 9.9% sales growth and new launches reached 5.7 billion euros in sales. We're pleased to have achieved another blockbuster milestone last year with Altubio. We successfully launched two new medicines, capillia for haemophilia, and weirils for ITP, and one vaccine, Novavaxivir, to protect against COVID-19. We also achieved several positive Phase III results, including most of the amlitalimab program in AD and the sarcleza subcutaneous formulation. Our innovation engine continues to make progress, replenishing Phase I, including three promising gene therapies, our entry into ophthalmology. Looking at Q4 performance on slide six, we delivered very strong results with 11.3 billion in sales and 13.3% growth, supported, of course, by our key drivers. Fitting to our launches on slide seven, I'm pleased to report that our newly launched medicines and vaccines grew 34% in 2025. Big Fortis continued to deliver with 1.8 billion euros in full-year sales, demonstrating the critical need for RSV protection. Altubio achieved blockbuster status, reaching €1.2 billion in full-year sales. Patient adoption continues to increase, with patients switching from both factor and non-factor medicines. Over note, Avakit reached $725 million in annual pro forma sales, slightly ahead of Blueprint's expectations from early 2025. Our newly launched medicines and vaccines demonstrate our commitment to innovation, and the strength of our commercial organisation. Moving to slide 8, we've picked and reached €4.2 billion in the quarter and €15.7 billion in annual sales. Continued growth across anchor indications and expansion into COPD, CSU and BP drove a more than 30% increase in patients over the past year. This underscores Dupixent's standing as the number one prescribed biologic across dermatologists, pulmonologists, allergists, and ear, nose, and throat specialists. The U.S. regulatory acceptance for the allergic fungal rhinosinusitis indication in November brings us closer to a potential ninth indication, further expanding Dupixent's reach. Turning to vaccines, we maintain our leadership in influenza and RSV despite a challenging environment. Full-year sales reached €7.9 billion. In influenza, we gained U.S. market share with the flu zone high-dose and flu block, while Europe saw continued penetration of efluelda and supanto. Big four has delivered a strong performance, growing 9.5% to €1.8 billion, ahead of our anticipated modest growth, and driven by geographic expansion across Europe and the rest of the world. With real-world evidence confirming 87-98% effectiveness, Mayfordus has protected more than 11 million babies in more than 45 countries, thus preventing an estimated 200,000 hospitalisations to date. We continue to strengthen our vaccines portfolio with strategic acquisitions that enhance our ability to protect older adults from serious diseases. In December, we completed the acquisition of Vice Bio, adding a bivalent RSV plus human metanumavirus vaccine candidate to our pipeline. This program complements our existing RSV franchise and leverages the innovative molecular clamp technology for vaccine antigen design. We also announced our proposed acquisition of Dynavax Technologies Corporation, which we expect to close in the first quarter this year. This acquisition adds Hepatitis B to our portfolio, the leading adult hepatitis B vaccine in the U.S. with a differentiated and convenient two-day schedule. It also brings a shingles vaccine candidate currently in Phase 1-2 studies, further expanding our pipeline in vaccines for older adults. These strategic additions reinforce our commitment to innovation in vaccines. Before moving to financials, I'm pleased to highlight Sanobi's key role in developing publicly available specification 2090, or past 2090, the first industry-wide global standard for measuring and reducing environmental impact of medicines and vaccines across their life cycle, recently published, by the way, in the British Standards Institution. We co-developed this harmonized framework with industry to enable eco-design for footprint reduction, accurate environmental reporting, while addressing growing stakeholder demands for transparency. Past 2019 marks an important moment for sustainable health care, showcasing how collaboration across the health care system can drive meaningful progress. True patient care means protecting not just individual health, but also planet health. This standard helps us to do both. Thank you. I'll now hand over to Francois, our CFO, for more details on the financials.

Thank you, Paul, and hello to everyone. Next slide, please. I'm pleased to report that we achieved our strongest quarterly sales growth in Q4 2025. Net sales grew by 13.3% to 11.3 billion euros. Dupixent delivered double-digit growth with continued penetration across all indications. Dupixent also benefited from a favorable basis of comparison due to growth to net price adjustments in the previous year. Business EPS growth was strong at 26.7%, reflecting our disciplined execution and operational leverage. Slide 14, please. Over the past three years, volume growth has accelerated and reached 34% on a compounded basis. Growth was driven by our successful launches and by Dupixent expansion across multiple indications, which continues to drive significant volume uptake eight years after the launch. Our ability to expand market reach while growing our margins demonstrate the strength of our innovation on our strong commercial execution. To meet growing patient demand and deliver on our MFN commitment, we will continue investing in manufacturing capacity with a strategic focus on the US. Next slide, please. Our full year 2025 results showcase the power of our business model, delivering strong growth with increased profitability. Sales reached 43.6 billion euros, representing 9.9% growth at constant exchange rates, at the upper end of our guidance. This represents a higher underlying growth level than in 2024, given that we excluded hyperinflation impacts from our sales growth at the beginning of 2025. Business growth margin expanded by 1.8 percentage points to 77.5%, driven by favorable product mix and operational efficiencies. Operating expenses increased by 7.9% as we increased R&D investments and supported our new product launches through sales and marketing investments. OPEX has decreased as a percentage of sales to 39.9% thanks to our efficiency programs. Business operating income increased by 11.9%, with BOI margin reaching 27.8%. Business EPS excluding share buyback grew by 12.2%, in line with our guidance, and including share buyback, our business EPS grew by 15%. This demonstrates our ability to grow EPS faster than sales, while investing in future growth. Moving to slide 16, our free cash flow has returned to strong levels in 2025 at 8.1 billion euros, representing 18.5% of sales. We aim to sustainably reach free cash flow of at least 20% of net sales in the medium term. This strong cash flow generation illustrates the quality of our earnings and the effectiveness of our working capital management, A key contributor to this performance was our inventory optimization, as we reduced inventory by nearly 30 days. We are targeting a similar inventory reduction in 2026, which will help us to progress toward our 20% free cash flow target. This disciplined approach provides us with significant financial flexibility to execute our capital allocation strategy. Next slide, please. We ended 2025 with a strong capital structure, as highlighted by our low net debt, which increased slightly to 11 billion euros. We maintained a conservative 0.8 times net debt to EBITDA ratio. This conservative leverage provides flexibility for future external growth opportunities, even while maintaining our double A rating. We successfully deployed the 10.4 billion euros received from the Opela divestment into value-creating business development and M&A opportunities, such as Blueprint, ViceBio, JointBio DR0201, Vigil, and some others as well. These divestments and acquisitions allowed us to accelerate our transformation as a biopharma company. Moving to the next slide, in 2025, we executed our capital allocation strategy across all four priorities. We significantly increased our organic growth investments in R&D, commercial capabilities, CAPEX and digital transformation. These investments fuel both current and future growth. As I just mentioned, we deployed the Opela proceeds into strategic acquisitions. We propose to increase our dividend for the 31st consecutive year to €4.12, up by 5% from the previous year. Finally, we completed our €5 billion share-by-back program. We will pursue our capital allocation policy in 2026. Regarding share-by-backs, we will execute a €1 billion share-by-back program in 2026. The consistency of this approach demonstrates our commitment to sustainable value creation and shareholder returns while investing in long-term growth opportunities. Looking ahead to 2026, we expect to deliver a year of profitable growth close to what we achieved in 2025. For the full year 2026, we guide for high single digit growth in sales and for profitable growth, meaning business EPS growing slightly faster than sales. Be aware that this guidance is for the full year 2026 and does not necessarily apply individually to each and every single quarter in 2026. Sales dynamics include further portfolio optimizations through divestments that will reduce sales by about 200 million euros in 2026. We expect vaccine sales to slightly decline in 2026. Our gross margin expansion is expected to continue with minimal tariff impact following the agreement reached with the US administration last December. Underlying R&D will increase moderately. In addition to this organic growth of R&D expenses, we have added a placeholder for potential future acquisitions, particularly for Phase 1 and Phase 2 assets. Sales and marketing expenses will increase to support growth and launches, while we continue to target stable G&A expenses. Our operating income is expected to include around €500 million of capital gains from this boson, As a reminder, the profit sharing line in RPNL is increasing faster than sales growth by more than 10 percentage points. We now expect a decrease of around 400 million in R&D reimbursement coming from Regeneron this year. This decrease will be more than offset by Amvutroy royalties, which are estimated at approximately 1 billion euros, based on the latest consensus. This results in a positive impact of around 500 million euros to BOI. Our financial outlook includes an increase of our financial expenses this year, driven by increased net debt from both 2025 and 2026 BD and M&A activities. Finally, we expect a stable effective tax rate. I now hand over to Oumam to provide an update on the progress of our innovative pipeline.

Thank you, François. 2025 has been a year of significant delivery across our pipeline. I'll walk you through the highlights. On pipeline delivery, we achieved 12 Phase 3 readouts and 15 Phase 2 readouts, and then added 10 new molecules to Phase 1, including three gene therapies, emphasizing our greater focus on research, supported by business development to replenish our early-stage pipelines. On the regulatory front, we obtained 20 regulatory approvals and 22 acceptances, including nine priority reviews, in addition to other designations, underscoring the progress we've made. Most importantly, we provided patients with three new medicines and vaccines. Cufitlia, the first RNAi antithrombin medicine in Haemophilia, approved in the US and China. Wayrills, the first PTK inhibitory in ITP, approved in the US and the EU, and our recombinant COVID-19 vaccine with full approval in the US and the EU. All these highlights represent meaningful progress in delivering transformative medicines and vaccines to patients worldwide. Please turn to the next slide. Turning to the Q4 highlights, where we received approvals including T-Pixen for CSU in the EU, T-Zield for stage 2 T1D in the EU, Weyrells for ITP in the EU, Serozine for Gaucher disease type 3 in the US. We strengthened our position in China with four approvals, something that I will return to again today. We received regulatory submission acceptance for T-Pixen for AFRS in the US, T-Zield stage 2 T1D for children in the US, and SP0087 rabies vaccine in the EU. On Phase 3 readout, amitilumab delivered more positive results in atopic dermatitis, and dupixent met its primary endpoint in AFRS. Tolabrutinib did not meet its primary endpoint in the PERSIS study for PPMS. As a result, we will not pursue its regulatory submission. Ending with typical Phase 3 start, we initiated the second-on-second-week study for COPD, two Duvatico studies, each in Crohn's disease and in ulcerative colitis, and one-way rills in IgG4-reducing disease. Next slide, please. I start with amlitilumab, whose recent data provides increasing confidence in progressive, long-term sustained benefit and patient convenience. Data across Phase 1, Phase 2, and Shore Phase 3 studies and the Atlantis Open Label Phase 2 study demonstrated progressively increasing efficacy over time, with no evidence of plateau for a week 24 to 52. This validates the potential for both monthly and quarterly dosing from the start, offering significant patient convenience as either monotherapy or combined with topical corticosteroids, an important background therapy used in the real world. amlitilumab was well tolerated with an acceptable safety profile. Much of our amlitilumab Oceana global atopic dermatitis program has now been delivered, including phase 2 and phase 3 studies evaluating its efficacy and safety when administered in monotherapy and in combination. Remaining studies are ACWA in patients with background TCS and TCI with inadequate response to biologic reject inhibitors, and Estuary, the randomized maintenance study. We expect both readouts in the second half of 2026, completing our comprehensive package for regulatory submission. Next slide, please. China remains a strategic priority, with significant progress made by our regional team. We obtained approvals for global medicines, Caplevi, anti-vomvuliparine factor antibody for acquired TTP, and Cufiblia. For China-only medicines, we received approvals for micorazone, for obstructive, obstructive high-profit cardiomyopathy, and for redempt plan in patients with familial myelomicronaemia syndrome. These approvals demonstrate our commitment to bringing innovative medicines and treatments to Chinese patients and to leverage Chinese innovation in doing so. Next slide, please. Let me share an update on our key mid- and late-stage pipeline projects. Our immunology pipeline has been strengthened by having delivered most of amyloid telomeres Phase III programs in AD, and Duvaticoq having advanced to Phase III for CD and UC. Lunsecumig will provide data on asthma this half and has potential for lifecycle opportunities. Rubecumig is now moving to Phase IIb. In neurology, colibrutinib is still under review for the EU-Fest DMS, for Xelomab and Phase III for RMS and S-DMS, and really through BART for Phase III for CIDP. The latter two with data already next year. In rare disease and oncology, Merrill-Wills is making progress with its life cycle planned beyond ITP. Vengola started in Phase III for GD3, data coming very soon, and Sarclisa expanding with a subcutaneous formulation. Our vaccines portfolio includes multiple programs across pneumococcal disease, yellow fever, meningitis, RSV, and pandemic preparedness. Next slide, please. On my last slide, I'll cover the 26 and 27 news flow, updates since December's year-end late-stage pipeline reviews. This year, we expect the remaining Phase 3 data for hamletilumab in AD and Phase 2 for linsecumic asthma, rare disease, the Bangla Stat Phase 3 readouts, if positive regulatory submissions will follow. We anticipate multiple regulatory submissions based on data we already received last and this year, as well as regulatory decisions for medicines and vaccines under review. Next year, we will get the Phase 2B data for provecimic, NHS, followed by Phase 3 studies of frexalamab and RMS, and really prove up in CIDP. My sincere thanks to all Sanofi R&D colleagues who share my commitment to advancing our pipeline from research to regulatory approval. This represents a rich, diversified news flow that we believe will continue to drive value creations for patients, society, and of course for Sanofi.

So we'll now open the call to questions. As a reminder, we'd like to ask you to send your questions to one or two each. You'll be notified when your line is open to ask your question. At that time, please make sure you unmute your microphone or, option two, submit your question by clicking the Q&A icon at the bottom of the screen.

Your question will be read by our panellists. Now we'll take the first question. Please go ahead.

The first question is from Zane Abraham from J.P. Morgan. Zane?

Hi there. Zane Abraham, J.P. Morgan. Thanks for taking my questions. My first question is on strategic picks and rollouts at CSU and COPD, which sound very They've been particularly strong. But can you elaborate on how those road arts are progressing and remind us of the biologic penetration in each of these indications and how Jepixent is faring against competition from Rapsido and CSU and Nucala and COPD? That's my first question. And my second question is a vaccines question. Just in terms of within your overall vaccines guidance, what you're assuming for Bay Fortis in 26 in terms of growth and how that looks for the US versus ex-US. Thank you.

Okay, same. Brian, do you pick something?

Thank you, Zane, so much for the question. So I'll go a bit broader, and then I'll focus in on a couple of those indications. So as you look at our performance in 2025, really strong performance, 25% growth year over year, and we culminated that with a really strong Q4, and I'll talk about that here in a minute, 32%. Now, this was driven not just based on those two indications that you highlighted, but the foundation of our indications grew as well, because it's a volume-driven growth story that we saw in 2025. Now, of course, those were on our base indications, but the launch of COPD, the launch of CSU, and the launch of BP were new sources of growth that were not in our base in 2024, which allowed us to accelerate growth, culminating actually in that Q4 that I talked about there just a bit. And I'll highlight COPD and CSU in just a minute. But that 32% growth that we saw at the end of the year is really a reflection of growth. those not being in our base but being strongly in Q4 performance that we saw. Now, as we go forward into 2026, we expect that growth to normalize, as we talked about, as we've seen before, and we're well on track to deliver our longer-term guidance by 2030 of greater than 22, around 22 billion sales. Now, specifically on COPD and CSU, I've spoken about COPD quite a lot. It was an inflection point for this year, as you can see from the performance, which was, again, being the first biologic, really the first innovative therapy in more than 10 years in the COPD space, and we've seen a really good response from the physicians. Now, remember, we were already in the pulmonologist offices with asthma and having the leading asthma therapy beforehand. So it was a really nice compliment. CSU is a very similar story. We've seen a really rapid uptake in the CSU launch. But again, remember, we were also already the leader in the dermatologist offices and the allergist offices with multiple indications, now eight indications in the U.S. So we've seen that those have contributed really nicely to our growth. Final point I'll make on CSU, because you asked a question about the competitors, Repsido, We don't really zoom in on one. We think competitors across all the immunology indications are really good because the biopenetration rates are extremely low. AD is only 18% still to date, and it's more than eight years into our launch. CSU, we believe, is in the low teens. So, again, this is a place where you're going to continue to see the market growth as well, which is great when we have new competitors come in.

Okay. Toma? Thank you, Zeyn, for the question. So as it comes to Befortus specifically, first of all, let me say that we are happy about the 2025 performance with an increase of a bit more than 9% year-on-year. When you recall very well that the Q2 earnings call, we had mentioned modest growth expectation for 2025. So happy about the performance. As you've noticed, it's a performance that's coming from broadening the reach to more and more countries, and Befortus is now available in more than 45 countries. So as we come to 2026 outlook, It's a bit tardy to be very specific on the performance of the product. However, I can say a few words about the dynamics. I think what's very important to have in mind is that there is a little bit of a different dynamic between U.S. and non-U.S. I think that's included in your questions. On the U.S. front, you have seen the recent changes on the pediatric immunization schedule. Still very recent. As you have seen from a recommendation perspective, nothing has changed for Bay Fortis in terms of recommendation or coverage. Now, will it create and to what extent confusion for parents and HCPs? I need to say, we need to see that in the coming years and in the coming months, sorry, and we'll be able to tell you a bit more at Q2 earnings call, more about B4TUS in the U.S. As of outside of the U.S., we will expand the geographic coverage as we've done over the past two years. And the last point I will refer to on B4TUS, For those that have not seen, there has been a very nice Chamba publication at the end of December 2025. This is the first real-world evidence head-to-head comparison between the use of either maternal immunization or passive immunization with Beportus. And you've seen that on very single endpoint, Beportus is doing better than the compilators.

Thank you very much. Thank you for that, Thomas. Next question, please.

Next question is from Ben Jackson from Jefferies. Ben?

Brilliant. Thank you for the question. Just two from me, please. I guess previously you've spoken about a range or numbers of peak sales estimates around amlitellamab. Perhaps now that we've had some additional data, has your view on any of this changed at all? And Hooman, perhaps if you could flesh that out. And you've had a little bit of time to talk to KOLs now and figure out how they're feeling. What is the feedback that you're getting on the additional results? not just kind of the positive parts on it too, but if I can push you, what are the pinch points? What are the bits that they've still got a little bit of uncertainty or questions over as well? And how can you address those? So just rounding that up would be brilliant. Thank you.

Thanks, Ben. Brian, do you want to give a sort of broad view?

Yeah, and thank you so much for the question, Ben. I think if you think about the broad view of this, and, again, remember that we were always bullish on this from an AD perspective, and I think Uman will probably talk about that. As you think about this marketplace, it's still really developing. We talked about the biopenetration I mentioned, 18%. It will more than double. I'm confident that it will more than double. If you look at what psoriasis has done, this is a marketplace that's going to continue to grow. And if you look at it today as new mechanisms come into the marketplace like we've seen, it actually accelerates the growth of the marketplace, much like psoriasis and so on and so forth. So having a new mechanism like this with a variety of areas in which to differentiate it, I believe, I mean, we remain extremely confident about the opportunity in that big marketplace.

Yeah, just to top and tell what Brian has said, I couldn't support more the importance of a novel mechanism in this space, which goes beyond a straightforward anti-cytokine blockade. Of course, that's an excellent mechanism in disease, but the addition of a T cell modulator with the promise, and I unlined the word, the promise of long-term immune normalization. It's obviously very attractive in the conversation. You are right to call out the importance of being more data-driven. And, of course, we've consistently shown a difference between this molecule that has a Q4 and Q12 dosing optionality, which means down to after loading dose four injections a year, which not only provides optionality for patients, but also site of injection, et cetera, which will matter. And also, both of those are really important, but I'd like to not only underline the importance of the mechanism and the optionality, but that this molecule remains aligned with our initial benefit risk assessment, which is ever so important in this space. which is hugely biologically underpenetrated. And Brian, at the very beginning of the call, outlined the importance of having options for these patients in terms of therapies. So finally, you asked discussions with prescribers. We did many hundreds of interviews over the last couple of years, including at the recent meeting in Paris. And I can genuinely say that there's enthusiasm about a novel mechanism for action in this space. Thank you very much for the question.

Thank you. Next question.

Yes. Next question is from Seamus Fernandez from Guggenheim. Seamus?

There we go. Let's try it again. There we go. Thanks so much. So just a couple of questions. The first one is on the kind of Kaposi sarcoma case that we saw. Can you provide a little bit more detail on that as it relates to amlitalimab? And, you know, is this – on mechanism in your view, or is it, you know, more a reflection of the, you know, sort of specific patient profile in that particular case? And just wanted to confirm that there were no and have been no additional cases seen in the overall program for amlitalimab. The second question is on Lincecumeg. I think you made a comment at a conference earlier this year specifically that There's a contribution of – that you believe there's a contribution of T-slip in some early atopic dermatitis data as it relates to linsecumig. I was just hoping you could clarify and confirm that comment and your views and hope that linsecumig, you know, in that formulation – in that disease state could potentially have a role. Thanks.

Thank you.

Multiple parts to that question. Number one, let me do the second one first, just to very quickly take that off the table. Yes, there is existing data, not with our molecule, but other people's molecules, that TSLP may indeed have a therapeutic benefit in the treatment of atopic dermatitis. Obviously, IL-13 is well established in this case. The combination of TSLP and IL-13 indeed may have an additive or indeed synergistic In fact, we are testing that clinical hypothesis. It will be very data-driven. So we look forward to seeing the results of lumbosecumab, not only in asthma and its related adjacencies, but also in atopic dermatitis. And then as you outlined in the Amelie question with the process of sarcoma, The answer to your question is that all immunomodulators come with a theoretical risk of infectious complications or increased infectious risk. Comparative sarcoma unequivocally is caused by a herpes virus, HHV-8, a standard herpes virus. And it's not surprising that a herpes virus would be associated with an immunomodulator as they are with all other immunomodulators. There is some genetic evidence suggesting Perhaps with amyloid filament, there may be a differential sensitivity to some or other of the herpes viruses. So, as you say, potentially our mechanism, the very first IV that we put out before we ever started the base three, this was anticipated and was not regarded as a significant improvement. issue of concern the benefit risk profile with this molecule is in line with everything we've said and as is our activity we will continue to produce not just with Kaposi sarcoma but all the broader safety and benefits of this molecule as we continue to publish uh the data uh sequentially until the end of the ocean studies thank you next question please next question is from david riesinger from lyrinc david

Yes, thanks very much. So congrats on the fourth quarter performance. I just have a couple questions. First, Hooman, in terms of the amletelemat press release that you issued recently, when do you expect to disclose full results from those studies? And, Francois, business EPS is expected to grow faster or slightly faster than sales this year, despite losing R&D reimbursement from Regeneron during the third quarter. Could you just talk about the offsets to that? And looking forward to 2027, how you're thinking about prospects for growth and earnings as well. Thank you.

Thanks, David. Yeah, quick answer to your question. I think we committed to presenting the Coast 1 data, AAD, which I think is at the end of March in Denver this year, subject to the Our conference organises Clement Nature. We may be able to put Coast to Ensure in there. That's still subject to discussion. So we hope to be able to present most of the data to you by the end of March.

Okay, thank you. François? Yes, David, as far as 2026 is concerned, to start with, indeed you mentioned it, we will have a decrease of the R&D reimbursement by Regeneron of 400 million this year. It was initially thought it would be 300, but since Dupixent is growing even faster than we thought, We will accelerate this determination of the reimbursement earlier. So we have a negative impact of 400 million this year, but it will be more than offset by the amputation royalties, which are going to increase even further than we thought. So we had almost half a billion of amputation royalties in 25. It will be probably around a billion in 26. So we'll have a net between the two items in terms of impact on the BOI of about positive 100 million this year in 26. In 27, we had initially thought that we would have the full impact of the termination of the R&D reimbursement by Regeneron. We expected initially that it would be a decrease of BOI for about 800 million in 27. It will be a bit less, probably with what we see today, around 700 million, as a consequence of what I said earlier. On Amvotra, it should be probably around, it's still early to say, but a further increase of 300 million, so the net between the two will be probably a negative in 27 at BOI level of minus 400 million, which is a bit better than what we had said last time.

Okay, thank you. Next question, please.

Yes, next question from Simon Baker from Redburn. Simon?

Thank you for taking my questions. Two if I may, please. Firstly, one for Hooman. You've had a bit of a rationalization of your phase two portfolio. I just wonder if you could talk us through any overarching principles that guided those decisions and future development plans. And then secondly, moving on to Depixent, the main patent goes in March 31. But as far as we can tell, you've got about 40 patents which expire between late 31 and February 2045. So I just wonder if you could give us your thoughts on life after March 31 in terms of the potential LOE for Depixen. Thanks so much.

Okay. Herman will get you in then, of course, quickly to Roy for his moment.

Anna, thanks for the question. When I started two and a half years ago, I was very clear that we'd have a dynamic allocation strategy. We are good stewards of capital, and we need to ensure that every dollar is well spent. So the overarching strategy, which Francois and I hold hands on, is that we will, on a regular basis, now on at least a quarterly basis, guided by AI, establishment of value will dynamically reallocate resources. And what that means is there'll be some programs that stop, but of course it also means that we will double down on some programs and we'll do the right things even if they're hard. So the overarching principle is very simply relation of capital allocation to value.

Thank you. Roy? So, Simon, thanks for the question. We do expect to PIXN to be protected by its patents beyond March 31 in the U.S. That's the reality, as you can imagine. Lots of innovation, lots of indications and counting. These are being recognized by multiple, and thank you for going through them, granted and to be granted patents ranging from 39.5% We believe we have a very strong patent portfolio, which we intend to vigorously defend. You'll understand it's too early to speculate on specific data by similarity. If and when patent fights commence, we'll be able to give you more details of what is being challenged and where, but we feel we're in a good place with Baltimore Patents.

Okay. Thanks, Roy. Okay. Next question, please.

Next question from Luisa Exel from Burenberg. Luisa? Hi there.

Thank you. I wanted to ask on vaccines, please, because if we look at 2025, you deployed about 3 billion euros on business development, M&A. So I wondered if you're putting that together with your R&D, is that a significant step up in capital allocation to vaccines? And how should we think about the opportunity cost versus building your drug pipeline? And then perhaps a little more color on Dynavax. It looks like a neat deal. So how did you value it? Is this a U.S. opportunity mainly? Is it catch up and then you move to an annual cohort eventually? And should we think about shingles as a booster opportunity in the over 70s? Thank you.

Thank you, Louisa. Thomas, two good questions for you.

So I will start in the reverse order with that in mind. So on Dynamax, let me first start by saying that the transaction is not closed yet. So as you know very well, we're still processing. But going back to your question, I can talk a little bit about the rationale. A few elements I'd like to highlight on this. First of all, it goes very well with what we have discussed before, with the fact that we are fairly present on a significant part of the pediatric immunization schedule. But as we discussed in the past, we see in terms of demographics simply an increase on the older adult group and a decrease over the past few years on the pediatric. And that's why our strategy is more and more focused towards the older adult group in terms of pipeline development. And the Dynavax proposed acquisition very well fits that profile with Eplisab V in FB mostly focused on the US. So that's really the cornerstone for this product with a very differentiated product with a two doses regimen versus three doses for any other competitor. And you've seen the progress on the market here. And we believe by adding our commercial muscle there, we can further improve the performance in this segment. In parallel, you have mentioned shingles. Very interesting phase 1-2 data there from the Dynavax shingles candidate. We believe there's a great possibility in terms of marketplace if there is a candidate that comes with a significant similar efficacy than the current incumbent in that place. However, with a much better tolerability, and we believe that the Dynavax technology will enable that profile. Going back to the first part of your question on capital allocation, so if you look at it from the way you framed it, indeed there has been an increase in 2025, but I'd like to maybe take a step back and explain to you how we look at it. We don't look at capital allocation or acquisition per tier. The way we look at it is what is the strategic fit of every single asset. or licensing it? Does it fit our portfolio? Does it fit our capabilities? Does it fit our long-term perspective on the business? We have a very strong long-term perspective on the vaccination business where the fundamentals are very strong. We believe that the acquisition we have made, both early and later stage in 2025, do reflect and do fit well that that perspective so we're not looking at it partially we're really looking at it what's the strategic fit what is are we the best owners can we deliver significant added value and if that's the case at the right price then we'll go for it thank you so much okay next question please yes next question from people from the yeah thanks people um bmp apologies if some of these questions have been asked but we've had a rather long

So just two questions. Thomas, sorry to stay on vaccines. Can we spend some time on the outlook in light of some of the recent developments that you've already touched upon, particularly in the US, and the context in terms of the 10 billion target you set for 2030? So just looking for a little bit of a ballpark reminder, what percentage of your business is exposed to these us pediatric vaccination schedule changes i know we're not expecting any imminent impact but just just to remind us what the ballpark exposure is could you flesh out a bit more some of the us and ex-us bay fortis dynamics and then when it comes to flu you know what's your sort of On a net basis, how are you thinking about the outlook? On one hand, you've got mRNA threats receding, but you've got investor concerns around risks from competitors to preventative assets rising. So net-net, how are you thinking about flu? That's the first question, and then much more succinctly, just pull off Francois, just on capital allocation, given the partner disappointments, is it fair to assume business development activity is set to accelerate significantly going forward? I realize you're not going to talk about specific assets, but just your intention to do BD, is that set to step change? Thank you.

Okay, thank you, Thomas and Francois.

Yeah, so for Welcome, first Pete, and indeed there was a bit of a similar question at the front stage, so I'll be pretty fast. So on the outlook about vaccines, and I think, to be clear and explicit, you're referring to the recent US childhood immunization recommendation changes in the US. Maybe a few words about this, and then we'll turn the page. So those recommendations, to be clear, have been pivotal in making sure that we can prevent life-threatening disease in US citizens for many, many decades. uh the recent and sudden shift there has been in early january to a three-tiered childhood vaccination framework uh who generate confusion for both parents and providers uh we don't know that uh we don't know yet if there will be a concrete impact in terms of this year that's way too early to look at that a couple of points though in terms of dynamics i'd like to highlight First of all, you've seen that several medical societies and by far the very, very vast majority of HCPs have decided to stick to the previous immunization schedule, first point. Second point, you have not missed the fact that all vaccines remain covered by insurance or by Medicare, depending on the different products. So it's not a question of coverage, but, Pete, you're right, there could be some confusions in terms of US PS3 vaccination schedule. The way we look at it is, what can we do? And we are focused on our energy and our actions. We engage proactively with HCPs, with Amicus societies, in every single country, US and non-US. We expand the benefits of our product, how they are differentiated from others, and we're focused on what we can do. So that's really for the situation in the U.S. You mentioned a couple of things on BEFORTUS, U.S. ex-U.S. We mentioned that in the call before, but as I was mentioning, happy about the 25% performance, 9.5% increase. 26% too early to say. We expect to give more guidance on this as we move forward in the year, probably at the QP earnings call, with then a look at U.S. versus ex-U.S. Your second point was on flu and how we look at the marketplace moving forward. You've seen that Q4 flu performance was significant. Maybe it's the opportunity for me to mention a couple of things. It's the second season in a row, two years in a row, two winters, where there has been a massive increase in terms of Influenza hospitalization across the northern hemisphere, on this side of the Atlantic or on the other side, which is a very important reminder of the fact that these cases can be prevented pretty simply with the vaccination, including with differentiated flu vaccination. Happy about our 2025 performance, which ends up showing that our market share will increase, especially thanks to our differentiated flu product. Fluzonido, which has shown great data again this year clinically, as well as Flublox, Flubantech, very important differentiators moving forward. Obviously, this comes in a very specific situation, i.e. a decrease in terms of VCR in the U.S. and a slight increase of influenza VCR in Europe, but you understand from a value perspective, these are very different markets. Moving forward, we'll probably give some more guidance on flu at the Q2 earnings call. mRNA on flu is not a concern for us for 2026. It will not be present. It's not a concern for us in 2027 neither, simply because, as we discussed before, people are looking for the right profile in terms of efficacy and tolerability profile. So we think we are well positioned. We have the right product. More to come after the pre-booking season, so probably around the Q20 score.

Thank you, Thomas. Francois? Yes, Friton. The capital allocation question, first and foremost, I presented it earlier. We have a strong balance sheet that gives us flexibility. That being said, we will remain very disciplined. So we will use our capital essentially around three criteria in terms of external growth, BD and M&A. Strategic, essentially around our four existing main surreptiting area plus potentially some white spaces. We want to make sure that we bring scientific differentiation with best-in-class, first-in-class assets and differentiated assets, and we want to secure financial return as well. We are certainly not chasing growth for the short and medium term. You saw our growth profile last year. You see our growth profile for 2026, which is at the upper end of the industry. So not chasing growth. But we are rather focusing on the longer term to complement our pipeline. So we have a certain number of assets in our pipeline. We know as well that we discussed it a few minutes ago. to manage the LOE of Dupixent at the earliest in 2031. We just discussed it. So as a consequence of that, we will try to focus essentially on phase one, phase two assets, which is our priority. We could as well, as we did last year, by the way, complement it with commercialized assets, which will probably to a certain extent mitigate the BOI slash EPS impact. Anyway, we will remain very disciplined. And I would not say we have time, because time flies and we have a feeling of urgency. But once again, we will be super focused and super disciplined. Thank you. Next question, please.

The next question is Keith Kala from TD Cohen. Keith?

Thank you so much. Two questions, please. First, I'm curious why Sanofi has not been as forthcoming as Regeneron on Dupixent lifecycle extension programs. I'm referring specifically to what Regeneron shared earlier this month. My understanding is that you have similar rights as you do now, so are you simply not as confident in those programs? So that's the first question. Second question is, in past quarters, Sanfi has noted on the Dupixent slide that Dupixent was number one in new-to-brand RX and number one in total brand share in the U.S. Curious why that was left off this quarter. Is that due to competition, specifically from Eblis? Thank you.

Okay, Brian, two questions for you.

I'll start with the second one. Steve, thanks. That's a really nice setup. Sorry we missed that on the slide. We are number one. We remain number one in every single indication across each of our specialists. So apologies. I think we are now adding more things about new indications and whatnot. We probably left that off there, but no. And I don't foresee that changing any time soon. Now, as it relates to LCM and forthcomingness from a Regeneron standpoint, I'll build on what Roy said. First, it starts with our IP. First, I have to think about that. How are we going to continue to defend that long into the future? And so Roy gave a statement there. So we've got quite some time. But we've been building along with the alliance and LCM strategy, as you would imagine, and we will reveal it in due course most likely the first half of this year you'll get an update on where we stand as far as what we're doing with dupixent specifically might be formulation related so on and so forth but you'll get a bit of an update there as well additionally we're working on next generation il4ra With Regeneron, Regeneron talked about this a little bit at J.P. Morgan, but we continue to work on and collaborate on programs that we have across the alliance. And, again, that can be really meaningful as a follow-on depiction and so on and so forth. But beyond that, given our success across the alliance for quite some time now, we're always open to and interested in considering future collaborations with Regeneron, as we said, at J.P. Morgan. So I feel like we're in a really good spot right now. More to come in the very near future. Thank you, Brian. Next question.

Next question from Sachin Jain from Bofa.

Hi there. Just two questions. Firstly, big picture, I guess, for Paul. There's a sentence in the press release that talks about mid-term profitable growth for five years, and at a recent conference you talked about potentially delivering, I guess, implied was Teams EPS. So just a big picture from your side, what was the intent on that signaling and giving consensus as a large of their X pipeline? So just thoughts as to inserting that commentary within the debate. for investors and then secondly one from human um do we get any further tl1a phase two data through the course of 26 that further profiles the asset as we start looking at phase three data i guess um into 28. thank you and this actually maybe transfer comment first from profitable growth yes profitable growth i think that uh we included that comment in the press release because we had a lot of questions we just wanted to make sure that the market understand that we do expect

to deliver an attractive level of growth to start with for the next six, potentially eight years. Who knows? And that this will be coming with profitable growth as well, because there was a question a couple of quarters ago about our capacity to deliver profitable growth each and every single year. I confirmed it a little bit earlier today. There was a question more specifically about 27, given the end of the R&D reimbursement with Regeneron, but it's not... or just a confirmation of the way that we see the outlook for the medium term. Thank you.

And your second question, the answer is simply yes. We will have maintenance data at some point this half. Thank you. Next question.

Yes, next question from James Gordon from Barclays. James?

Hello, James Gordon from Barclays. Thanks for taking the questions. One question was on business development. I know you've had some questions on this already, but a follow-up to those, please. I've seen some attributive comments this morning about the company having a 14 to 15 billion euro BD firepower amount for this year. And assuming that is right, and that was the comment, what is the thinking there? Is it that you can really fire that immunology to get more assets, a good complement, a follow-on from DuPy? Or with immunology looking a bit crowded and you've got a lot going on in immunology anyway, already and a bit more competition coming as well, could you focus beyond 2P and say, right, we're going to broaden out other areas of the business? So could it be like 15 billion on one big deal? And if so, is it more likely to be trying to do even more immunology or could you diversify? I didn't see an update in the regulatory plans. Have you now spoken to the FDA, or if not, when will you? And do you think you can file on the data you've got? Thanks.

Why would you transfer them in?

No, no, I will answer on the 15 billion, which is, I would say, the upper limit of what we can do to maintain our WRIT. It has nothing to do with where we can invest by TA and so forth. As I said, I mean, we are interested fundamentally in strengthening our position in our four existing TAs plus potentially wide spaces. We could always contemplate going further than that. But the $15 billion was the, let's say, technical limitation to preserve our double A rating. Thank you.

Yeah, I'll follow Brian's lead. Thank you for the setup. We had... Excellent data, as we announced late last year. We'll imminently, certainly this half of the year, go to the FDA to have broader conversations on the trajectory of that molecule, as we'd previously suggested.

Thanks for the question. Okay. I think this is the final question, is it? Or at least the next question?

Yes, next question from James Quigley from Goldman Sachs. James?

Perfect. Thank you for my questions. I've got two, please. Hopefully they haven't already been asked, but I'll give it a go anyway. So firstly, following on from Steve's question on the Regeneron portfolio, the the ir13 assets were not in the alliance so was that a was that a sanitary decision so is it that you think the second is more attractive option for io13 can you give us any color yet as to why you're excited about the ir13 and t-slip combination for the second week and then secondly on the computer portfolio Our TVO continues to show strong growth. What are your expectations here into gaining additional share into 2026? Are you willing to give a peak sales forecast here now that you've hit blockbuster status? And also for Cufilia, the launch is progressing steadily. You've got China approval now. So what's the feedback been in terms of where Cufilia is being used? Are there any lingering thrombosis concerns with the product that may be holding it back? Thank you.

Okay. Thank you so much. Okay. Brian, over to you.

Yeah. James, thanks so much for the question. I briefly addressed it just before. So not a decision necessarily on the IL-13. I think we talked about this a little bit at J.P. Morgan not so long ago. But as I said before, we are – it's not in the alliance currently, but we're always open to having conversations with the general about potentially including it in the alliance. As I also said, we have a long-acting IL-4R. or any that actually is in the alliance that we're actually working on right now as a follow-on asset to Defilamab. So, again, long-withstanding great partnership with Regeneron, so we'll always have conversations with them about what we might do next together. As it relates to Kefilia, you want me to tackle the Kefilia one next? Kefilia is, again, it's still early days as far as the launch goes. We said from the very beginning this is really – Very cool therapy in the sense that it is very targeted, kind of precision medicine, if you will, comes with a diagnostic as it relates to antithrombin levels. And, again, what we said is we'll have a little slower ramp. I think it will be a lot stickier on the back end from a patient standpoint as physicians get really they can dial it up and dial it down as the patient presents and it's really more personalized by each patient. So far we've heard really good feedback from the marketplace. No concerns as far as safety goes so far, but, again, it's early days and promising. We'll keep you up to date in future calls.

Okay, thanks, Brian. And then I think there may be one more.

Yeah, one more question, and last question from Bram Barry, from CT, Bram.

Great. Thanks, excuse me, and apologies if it has been asked, but I think it has. I just want to check on itotecumab. You're saying about looking at additional data for the path forward. So can you give us timelines on what it is you're looking on the data and the clarity and timelines on path forward for that molecule? And then tolabutinib in the U.S., are we just correct to assume no path forward in the U.S.? If you could just comment on rest of world regulators' attitudes to the ability to monitor compared to the U.S., that would be very useful. Thank you.

Graham, at Citi, and those that will know, know I have made that point. Thank you for the question. The first question, let me do it in reverse, Tala Brutnibs, approach is pretty straightforward. We're waiting for regulatory comments from the rest of the world, as you say, from EU, and we'll see where we take it from there. And then on the spec map, as I've consistently said, The next step will be determined by interactions with the FDA predominantly to establish exactly the requirements for a replication study for Phase 3 going forward. As soon as we know, we will commit to sharing it more broadly in partnership with our successful alliance partners with Gemma.

Okay. Thank you, Eamonn. Thank you, Graham.

Well, thanks for this last question. In 2025, we achieved a strong year of profitable growth. Sales increased by 9.9% with constant exchange rates, while business EPS improved significantly faster by 15%. We launched three new medicines and vaccines, Cutipia, Wayvils and Invexavid. All this was made possible by the dedicated effort of all Sanofi colleagues worldwide. In 2036, we expect sales to grow by a high single-digit percentage. and business EPS to grow slightly faster than sales. We anticipate profitable growth to continue over at least five years. Based on our pipeline, combined with external growth opportunities, our ambition is to pursue earnings growth into the next decade. With this, I would like to thank you for the interest in Sanofi, and we'll now close the call.

Thank you.